This is a comprehensive study of interferon (IF) and double-stranded RNA (dsRNA) as a total system in both human and Syrian hamster cells. There are five major projects: (1) Function and structure relation of dsRNA as related to its involvement in the induction, action, and regulation of interferon and its intrinsic effects on cells. Extensive chemical modification of dsRNA and the use of anti-IF antibody are the strategy of this project; (2) The structure and function of 2'-5' oligo adenylic acid through the investigation of analogs. Analogs of 3'-deoxyribose and 3'-O-methylribose backbone have already been synthesized. The effects of these analogs on the 2'-5' oligo A activated reactions both in vitro and in vivo may provide unique insight on the role of 2'-5' oligo A in living cells; (3) Antineoplastic effects and antiproliferative effects of IF/dsRNA: Suppression of the expression of neoplastic phenotypes, suppression of progression in neoplastic transformation, and suppression of growth of normal versus tumorigenic cells will be investigated. Our very extensive experiences, accomplishments, facilities, and materials in in vitro carcinogenesis of hamster cells as well as in two human tumor cell lines will be the basis of this study; (4) The expression and influence of IF system in embryogenesis - Early results and literature reports indicate that the genes governing the IF system are being expressed during embryogenesis. This investigation of this differentiation system will provide insight on the relationship between various in vivo biological expressions and the in vitro biochemical reactions in the IF system, as the IF system is being developed from a dormant stage to an operational stage; (5) Somatic cell hybridization and somatic mutation studies of the IF system - In addition to the selection of variants/mutants resistant to the antineoplastic and antiproliferative effects of IF/dsRNA, somatic cell hybrids and mutants will be obtained for the studies on the IF regulation-shutoff systems. The research in the first year will be concentrated mainly on Projects 1, 2, and 3, and Project 4 and 5 will be investigated in subsequent years. Knowledge obtained from this research is vital for the use of IF as antiviral and anticancer drug, and may also greatly enhance human IF production for practical use.